The objectives of this research are (1) to cultivate Mycobacterium leprae in tissue culture and (2) to establish long-term generalized M. leprae infection in neonatally thymectomized Lewis rats (NTLR) so they can serve as sources of M. leprae for the tissue culture studies and as animal models for the study of leprosy, particularly in the evaluation of chemotherapeutic agents. We have tested tissue cultures from a variety of mammals for their ability to support multiplication of M. leprae. These have included tissues from mammals with a low body temperature as well as tissues from cool sites on mice, rats, and humans. Although survival of M. leprae could be demonstrated for up to 118 days, no multiplication could be demonstrated. The studies will continue with tissue cultures from other mammals known to be susceptible to M. leprae infection. Various regimens of drug treatment have been initiated on chronically infected NLTR. Preliminary evidence indicates that combinations of ineffective dosages of various drugs have a synergistic effect when given simultaneously and result in a greatly enhanced killing effect on M. leprae. These studies will be continued to determine the most effective combination and dosage of drugs.